CIMDUO® (lamivudine and tenofovir disoproxil fumarate) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 35 kg.
WARNING: POST TREATMENT ACUTE EXACERBATIONS OF HEPATITIS B
Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine or tenofovir disoproxil fumarate, components of CIMDUO. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment [see Warnings and Precautions (5.2)].
IMPORTANT SAFETY INFORMATION
CIMDUO is contraindicated in patients with a previous hypersensitivity reaction to any of the components contained in the formulation.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
All patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Discontinuation of anti-HBV therapy, including lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), may be associated with severe acute exacerbations of hepatitis. Patients infected with HBV who discontinue CIMDUO should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted. See the full prescribing information for Important Differences Among Lamivudine-Containing Products.
TDF, a component of CIMDUO is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF.
It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy and as clinically appropriate during therapy with TDF. In patients at risk of renal dysfunction, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of TDF, and periodically during TDF therapy.
CIMDUO should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)).
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as 3TC, a component of CIMDUO. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with 3TC in HIV-1/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and 3TC should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. See the full prescribing information for interferon and ribavirin.
In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, 3TC, a component of CIMDUO, should be used with caution. Treatment with CIMDUO should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.
In clinical trials in HIV-1 infected adults, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown.
Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of TDF.
Immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy, including 3TC and TDF
In HIV-infected patients, redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving combination antiretroviral therapy.
Early virologic failure has been reported in HIV-infected patients treated with triple nucleoside-only regimens. Monitor carefully and consider treatment modification.
The most common adverse reactions (> 10% with CIMDUO) are headache, pain, depression, diarrhea, and rash.
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CIMDUO® is a registered trademark of Mylan Pharmaceuticals Inc. MYLAN and the Mylan logo are registered trademarks of Mylan Inc. All other trademarks and service marks are the property of their respective owners.